The long term goal of this research proposal is to design an effective and safe vaccine adjuvant for human administration. Specifically, we will study the adjuvant effects of liposome carriers containing an immunomodulator, muramyltripeptide-phosphatidyl-ethanolamine (MTP-PE). We have observed a markedly enhanced presentation, in vitro, of the antigen, HSV recombinant glycoprotein D (rgD), leading to in vivo immunotherapeutic effects in recurrent herpes simplex genitalis in guinea pigs. We will optimize the variables for use of these liposomes (collectively called antigen presenting liposome, APL) with HSV recombinant proteins, specifically rgD and rgB for immunotherapeutic treatment of HSV infection. Such variables include the use of various types of carriers, immunomodulators and variations in the antigen structure for the optimum adjuvant effect of antigen presenting vehicles (APV). In order to design an effective adjuvant, it is important to understand the immune mechanisms by which APV enhance immunotherapeutic effects. Therefore, we will elucidate the pathways by which APL (with MTP-PE) potentiate adjuvant effects of our HSV recombinant antigen. These studies will probe the immunotherapeutic effects in vivo, using the guinea pig model, and in vitro, using both guinea pig and human lymphocytes. The findings from this work will be utilized in designing an effective and safe adjuvant for HIV proteins. Since the enhancement of lymphocyte stimulation provided by APL in vitro parallels and improved clinical efficacy in the guinea pig HSV recurrence model, we propose to evaluate the adjuvant activities of the APV on the peripheral blood lymphocytes isolated from asymptomatic HIV-infected patients using molecularly cloned HIV antigens. Parallel experiments will also be done with HIV-infected chimpanzees that exhibit cellular immune responses to HIV antigens.